Generalizability of Progression Risk in the TN-10 Trial to a European Population With or Without a First-Degree Relative With Type 1 Diabetes.

Abstract

In the TrialNet 10 Anti-CD3 Prevention (TN-10) trial, teplizumab delayed onset of stage 3 type 1 diabetes in U.S. and Canadian individuals with stage 2 disease who had a relative with type 1 diabetes. Here, the generalizability of the population risk in TN-10 to a European population with or without first-degree relatives (FDRs) with type 1 diabetes was investigated. This retrospective study used data from participants with stage 2 type 1 diabetes from the TN-10 placebo arm and the Fr1da population-based screening program in Germany (Fr1da group) to investigate time to progression from stages 2-3 type 1 diabetes. The study only had sufficient power to detect large differences. Risk of progression to stage 3 type 1 diabetes was comparable between the TN-10 placebo arm (n = 32) and the Fr1da group (n = 152; hazard ratio [HR] = 1.3 [95% CI 0.8-2.1]). Once prognostic factors significantly associated with progression in this study (anti-IA-2 antibodies, HbA1c >5.7%, and 120-min oral glucose tolerance test) were included in the model, the adjusted HR was 1.1 (95% CI 0.6-2.1). Fr1da group participants with (n = 45) and without (n = 107) FDRs with type 1 diabetes had similar time to progression to stage 3. Age-based subanalysis demonstrated minimal impact of age on progression time. Time to progression to stage 3 appeared similar between the TN-10 placebo arm and the Fr1da group and between participants with and without FDRs with disease. Results suggest progression risk from the TN-10 trial may be generalizable to European populations with or without FDRs with type 1 diabetes.